Sepsis and septic shock represent the most common cause of death in ICU patients. The most characteristic hemodynamic finding in septic shock patients is a decreased systemic vascular resistance (SVR). The cause of this decreased SVR is not known; however, complement activation with projection of C5a may be involved. C5a is a known anaphylatoxin that can cause mast cells to release vasoactive mediators. Serial serum samples for various complement components were drawn from patients with septic shock and correlated with simultaneous hemodynamic determinations. Serum C5a was found to be abnormal more commonly than other complement components in these patients. C5a was found to be abnormal in patients with blood culture positive septic shock and blood culture negative septic shock; it was never elevated in hypovolemic or cardiogenic shock. The elevated C5a levels significantly correlated (negatively) with systemic vascular resistance index, indicating a possible role for the known anaphylotoxin C5a in the complex pathogenesis of septic shock. The association of complement component abnormalities is now being correlated with specific complications of septic shock and with prognosis.